Carmen González-Keelan

Breast cancer molecular subtypes and survival in a hospital-based sample in Puerto Rico

Information on the impact of hormone receptor status subtypes in breast cancer (BC) prognosis is still limited for Hispanics. We aimed to evaluate the association of BC molecular subtypes and other clinical factors with survival in a hospital‐based female population of BC cases in Puerto Rico. We analyzed 663 cases of invasive BC diagnosed between 2002 and 2005. Information on HER‐2/neu (HER‐2) overexpression, estrogen (ER), and progesterone (PR) receptor status and clinical characteristics were retrieved from hospitals cancer registries and record review. Survival probabilities by covariates of interest were described using the Kaplan–Meier estimators. Cox proportional hazards models were employed to assess factors associated with risk of BC death. Overall, 17.3% of BC cases were triple‐negative (TN), 61.8% were Luminal‐A, 13.3% were Luminal‐B, and 7.5% were HER‐2 overexpressed. In the multivariate Cox model, among patients with localized stage, women with TN BC had higher risk of death (adjusted hazard ratio [HR]: 2.57, 95% confidence interval [CI]: 1.29–5.12) as compared to those with Luminal‐A status, after adjusting for age at diagnosis. In addition, among women with regional/distant stage at diagnosis, those with TN BC (HR: 5.48, 95% CI: 2.63–11.47) and those HER‐2+, including HER‐2 overexpressed and Luminal‐B, (HR: 2.73, 95% CI:1.30–5.75) had a higher mortality. This is the most comprehensive epidemiological study to date on the impact of hormone receptor expression subtypes in BC survival in Puerto Rico. Consistent to results in other populations, the TN subtype and HER‐2+ tumors were associated with decreased survival.

Serum vitamin D and colonic vitamin D receptor in inflammatory bowel disease

AIM To determine serum vitamin D levels and colonic vitamin D receptor (VDR) expression in inflammatory bowel disease (IBD) and non-IBD patients and correlate these with histopathology. METHODS Puerto Rican IBD (n = 10) and non-IBD (n = 10) patients ≥ 21 years old scheduled for colonoscopy were recruited. Each patient completed a questionnaire and provided a serum sample and a colonic biopsy of normal-appearing mucosa. For IBD patients, an additional biopsy was collected from visually diseased mucosa. Serum vitamin D levels were measured by ultra-performance liquid chromatography and mass spectrometry. Hematoxylin and eosin stained tissue sections from colonic biopsies were classified histologically as normal or colitis (active/inactive), and scored for the degree of inflammation present (0-3, inactive/absent to severe). Tissue sections from colonic biopsies were also stained by immunohistochemistry for VDR, for which representative diagnostic areas were photographed and scored for staining intensity using a 4-point scale. RESULTS The IBD cohort was significantly younger (40.40 ± 5.27, P < 0.05) than the non-IBD cohort (56.70 ± 1.64) with a higher prevalence of vitamin D deficiency (40% vs 20%, respectively) and insufficiency (70% vs 50%, respectively). Histologic inflammation was significantly higher in visually diseased mucosa from IBD patients (1.95 ± 0.25) than in normal-appearing mucosa from control patients (0.25 ± 0.08, P < 0.01) and from IBD patients (0.65 ± 0.36, P < 0.05) and correlated inversely with VDR expression in visually diseased colonic tissue from IBD patients (r = -0.44, P < 0.05) and from IBD patients with Crohns disease (r = -0.69, P < 0.05), but not in normal-appearing colonic tissue from control patients or IBD patients. Control and IBD patient serum vitamin D levels correlated positively with VDR expression in normal colon from control and IBD patients (r = 0.38, P < 0.05) and with patient age (r = 0.54, P < 0.01). CONCLUSION Levels of serum vitamin D correlate positively with colonic VDR expression in visually normal mucosa whereas inflammation correlates negatively with colonic VDR expression in visually diseased mucosa in Puerto Rican patients.

Immunohistochemical expression of SP-NK-1R-EGFR pathway and VDR in colonic inflammation and neoplasia

AIM To determine the expression of neurokinin-1 receptor (NK-1R), phosphorylated epidermal growth factor receptor (pEGFR), cyclooxygenase-2 (Cox-2), and vitamin D receptor (VDR) in normal, inflammatory bowel disease (IBD), and colorectal neoplasia tissues from Puerto Ricans. METHODS Tissues from patients with IBD, colitis-associated colorectal cancer (CAC), sporadic dysplasia, and sporadic colorectal cancer (CRC), as well as normal controls, were identified at several centers in Puerto Rico. Archival formalin-fixed, paraffin-embedded tissues were de-identified and processed by immunohistochemistry for NK-1R, pEGFR, Cox-2, and VDR. Pictures of representative areas of each tissues diagnosis were taken and scored by three observers using a 4-point scale that assessed intensity of staining. Tissues with CAC were further analyzed by photographing representative areas of IBD and the different grades of dysplasia, in addition to the areas of cancer, within each tissue. Differences in the average age between the five patient groups were assessed with one-way analysis of variance and Tukey-Kramer multiple comparisons test. The mean scores for normal tissues and tissues with IBD, dysplasia, CRC, and CAC were calculated and statistically compared using one-way analysis of variance and Dunnetts multiple comparisons test. Correlations between protein expression patterns were analyzed with the Pearsons product-moment correlation coefficient. Data are presented as mean ± SE. RESULTS On average, patients with IBD were younger (34.60 ± 5.81) than normal (63.20 ± 6.13, P < 0.01), sporadic dysplasia (68.80 ± 4.42, P < 0.01), sporadic cancer (74.80 ± 4.91, P < 0.001), and CAC (57.50 ± 5.11, P < 0.05) patients. NK-1R in cancer tissue (sporadic CRC, 1.73 ± 0.34; CAC, 1.57 ± 0.53) and sporadic dysplasia (2.00 ± 0.45) were higher than in normal tissues (0.73 ± 0.19). pEGFR was significantly increased in sporadic CRC (1.53 ± 0.43) and CAC (2.25 ± 0.47) when compared to normal tissue (0.07 ± 0.25, P < 0.05, P < 0.001, respectively). Cox-2 was significantly increased in sporadic colorectal cancer (2.20 ± 0.23 vs 0.80 ± 0.37 for normal tissues, P < 0.05). In comparison to normal (2.80 ± 0.13) and CAC (2.50 ± 0.33) tissues, VDR was significantly decreased in sporadic dysplasia (0.00 ± 0.00, P < 0.001 vs normal, P < 0.001 vs CAC) and sporadic CRC (0.47 ± 0.23, P < 0.001 vs normal, P < 0.001 vs CAC). VDR levels negatively correlated with NK-1R (r = -0.48) and pEGFR (r = -0.56) in normal, IBD, sporadic dysplasia and sporadic CRC tissue, but not in CAC. CONCLUSION Immunohistochemical NK-1R and pEGFR positivity with VDR negativity can be used to identify areas of sporadic colorectal neoplasia. VDR immunoreactivity can distinguish CAC from sporadic cancer.

Abstract LB-325: Characterization of triple negative breast cancer patients among Hispanics in Puerto Rico

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Introduction: Hormone receptor status had been correlated with prognosis in breast cancer patients. Breast cancer patients with no expression of estrogen receptor (ER), progesterone receptor (PR) and her-2 neu (her-2) have been grouped in the Triple Negative Breast Cancer (TNBC) category. At present, these patients have very limited adjuvant therapy alternatives. TNBC has been correlated with poor prognosis among African-American and Hispanic populations. However, there is very few data regarding the prevalence and characterization of TNBC among Hispanics groups (e.g. Puerto Ricans, Cubans, etc.). The objective of this study is to characterize the TNBC population among the Puerto Rican population and to assess whether expression of ER changes the characteristics of the disease in this group. We hypothesize that expression of ER+ in her-2 negative breast cancer tumors will change the initial presentation of the disease. Methods: This cross-sectional study analyzed data from female patients with breast cancer diagnosed between 2000 and 2005, at the I. Gonzalez Martinez Hospital and the Auxilio Mutuo Hospital (n=1,082) in San Juan, Puerto Rico. Information on Her-2 status and other clinical characteristics were retrieved from the hospitals cancer registries and from medical record review. This study was approved by the Institutional Review Boards of the participating hospitals. Logistic regression models were used to evaluate the associations between relevant clinical characteristics and TNBC. We also evaluated whether there were any interaction between age, tumor size and receptor status. Results: The prevalence of TNBC in our study was 16.3% and 58.7% for the Her-2-ER+s phenotype. Patients in the TNBC group have a younger age ( 2cm) (70.3% vs 45.6%), invasive ductal histology (87.3% vs 68.7%), and higher tumor grades (III-IV) (49.7% vs 13.2%) compared to Her-2-ERs+. Using multinomial models, we found that, compared to TNBC, women with Her-2-ER+PR- and those with Her-2-ER+PR+ were 1.99 (CI95%=1.15,3.44) and 1.66 (CI95%= 1.11, 2.46) times more likely to have > 50 years at diagnosis as compared to those with 2cm. There was no interaction between receptor status, age and tumor size (p=0.582). Conclusions: TNBC in Hispanics from Puerto Rican origin showed the same prevalence of Hispanic women in California. Furthermore, disease characteristics (early age at diagnosis, tumor size, histology and tumor grade) were also similar, suggesting that race has a significant effect in the presentation of TNBC in Hispanic women. In addition, the expression of ER, but not PR in Her-2 negative patients dramatically changes the initial presentation of the disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-325. doi:1538-7445.AM2012-LB-325

Abstract 873: Prevalence and correlates of HER2/neu overexpression among invasive breast cancer cases in two hospitals in Puerto Rico

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Introduction Breast cancer (BC) is the most common female malignancy in Puerto Rico. Cases with human epidermal growth factor receptor 2 (HER-2)/neu oncoprotein overamplification are consistently associated with poor prognosis, poor response to endocrine treatment, and an increased likelihood of recurrence. The objective is to evaluate the prevalence of HER2 /neu gene overexpression among a hospital-based female population of BC cases in Puerto Rico, and to determine its association with other clinical characteristics. Methods This cross-sectional study analyzed data from female patients with invasive BC diagnosed between 2000 and 2005, at the I. Gonzalez Martinez Hospital and the Auxilio Mutuo Hospital (n=1,082) in San Juan, Puerto Rico. Information on Her-2 status and other clinical characteristics was retrieved form the hospitals cancer registries and from medical record review. This study was approved by the Institutional Review Boards of the participating hospitals. Logistic regression models were used to evaluate the associations between relevant clinical characteristics and Her-2 status. Results: The prevalence of Her-2/neu overexpression in our study aas 20.9%, whereas 72.3% of the cases were ER positive and 59.3% were PR positive. In multivariate analysis, women with an age at diagnosis ≤ 50 years were 1.74 (95% CI=1.26-2.41) times more likely to be Her-2 positive as compared with those with an age at diagnosis ≥ 50 years. Regarding ER/PR status, women with ER+/PR- and those with ER+/PR+ were 1.97 (95% CI=1.30-2.98) and 2.15 (95% CI=1.49-3.10) times more likely to be Her-2 positive as compared to those with ER-/PR- status. Finally, women with invasive ductal histology were 1.79 (95% CI=1.08-2.95) more likely to be Her-2 positive as compared to those with invasive lobular histology. Women with tumor grade III/IV, tumor size ≥ 2 cm and lymph node metastasis were also more likely to be Her-2 positive (p<0.05). Conclusions: The prevalence of Her-2/neu overexpression in this population of Puerto Rican patients (20.9) and its association with earlier age at diagnosis, tumor size, lymph node metastasis and other clinical characteristics shows that BC patients with Her-2 positive tumors followed similar profiles as Her-2 positive BC patients in the US population. Results from this study will be useful for the development of future BC prevention and control strategies in Puerto Rico. Sponsors: This work was supported by an unrestricted grant from Glaxo SmithKline with additional support from the National Institutes of Health and National Center for Research Resources (NCRR) [grant number G12RR03051 and U54CA96297]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 873.

Abstract B57: Breast cancer subtypes and survival in a hospital-based sample in Puerto Rico

Introduction: Breast cancer is the most common female malignancy in Puerto Rico and the United States. Breast cancer is a multifaceted disease comprised of distinct biological subtypes with diverse etiology, therapeutic indications and clinical outcomes. Information on the impact of hormone receptor status sub-types in disease prognosis is still limited for Hispanics. To overcome this limitation, we aimed to evaluate the association of breast cancer subtypes and other clinical factors with breast cancer survival in a hospital-based female population of breast cancer cases. Methods: We analyzed data from female patients with invasive breast cancer diagnosed between 2000-2005, at the I. Gonzalez Martinez Hospital and the Auxilio Mutuo Hospital (n=974). Information on Her2/neu (Her2) overexpression, Estrogen receptor (ER) and Progesterone receptor (PR) status and other clinical characteristics was retrieved from the hospitals’ cancer registries, the Puerto Rico Central Cancer Registry and from medical and pathology record review. Survival by covariates of interest was estimated using the Kaplan-Meier method, and survival curves were compared using the Wilcoxon test. Multivariate Cox proportional hazards models were employed to assess factors associated to breast cancer survival. Results: Overall, 22.5% of breast cancer cases were Her2+, 16.6% were triple negative (ER-/PR-/Her2-) and 60.9% were Her2-/ER+ or PR+. Factors associated to breast cancer death in bivariate analyses included younger age at diagnosis ( 0.05). Meanwhile, women with regional (HR=1.83, 95% CI: 1.29-2.61) and distant (HR=9.21, 95% CI:4.94-17.17) disease at time of diagnosis had higher risk of death as compared to those with localized disease. In multivariate analysis, Her2 positivity was still not associated with breast cancer mortality after adjusting for age and stage at diagnosis (HR=1.22, 95% CI:0.83-1.78). Meanwhile, women with triple-negative breast cancer had higher risk of breast cancer death after adjusting for age and stage at diagnosis (HR=2.65, 95% CI:1.80-3.88). Conclusions: This is the most comprehensive epidemiological study to date on the impact of hormone receptor expression sub-types in breast cancer survival in Puerto Rico. The clinical correlates of breast cancer survival in this population follow the same trends described previously in US populations. Even though no significant differences in survival were observed by Her2 overexpression status, consistent to results in other populations, the triple negative subtype was associated with decreased survival. The results of this study are useful for the development of breast cancer control strategies in Puerto Rico. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B57.